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Virus may thrive in lining of sex organs: Seventh International Conference on AIDS held in Florence last week

29 June 1991

By PHYLLIDA BROWN and DAVID CONCAR

Cells in the linings of the sex organs and the anus can harbour HIV
and allow it to replicate rapidly, according to American researchers. This
unexpected finding, reported in Florence, may help to explain how the virus
spreads from person to person during intercourse.

Dani Bolognesi, a leading AIDS vaccine researcher from Duke University,
North Carolina, said the results were important because of the ‘strategic
position’ of the cells on the virus’s main routes of entry to the body.
William Haseltine from the Dana-Farber Cancer Institute in Boston, whose
team carried out the study, said the findings reinforce the message that
HIV is basically a sexually transmitted disease.

Although sex is the most important route of transmission for HIV, it
is the least understood. Eight out of 10 infections are acquired through
intercourse rather than via the bloodstream or in pregnancy, but researchers
know almost nothing about which cells in the genitals are involved. Many
scientists believed until now that blood must be present – even in very
small quantities – for HIV to be transmitted.

The new findings suggest they were wrong. Erik Langhoff, Haseltine and
others from the Dana-Farber Cancer Institute have carried out laboratory
studies on white blood cells called dendritic cells. The immature forms
of these cells are found on all the mucous membranes – the body’s front
line of defence against the outside world. Scientists believe that the function
of the cells is to carry foreign proteins from the mucous membranes through
the bloodstream to meet the T cells of the immune system, which destroy
them.

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To their surprise, Langhoff and his colleagues found that HIV grew much
faster in immature dendritic cells than in the cells known to be its usual
targets, the CD4 lymphocytes and macrophages. The team also found that only
low concentrations of the virus were needed to infect the dendritic cells.
In culture, the cells produced between 20 and 40 times as much virus as
HIV’s other target cells and, unlike these others, they survived infection.

All the scientists at the conference had a warning about such laboratory
studies: research on cultured cells should not be taken as gospel without
additional evidence from living animals or humans. To culture cells is to
disturb them, said Simon Wain-Hobson from the Pasteur Institute in Paris.

But support for Langhoff’s findings comes from the study of monkeys
infected with simian immunodeficiency virus, the nearest animal equivalent
of HIV. Christopher Miller and his colleagues at the California Primate
Research Center found infected dendritic cells in the epidermis of macaques’
penises. They also found infected CD4 lymphocytes and macrophages throughout
the sex organs of male and female monkeys, including the foreskin of the
penis.

Despite the progress, important questions remain about sexual transmission.
How infectious is semen, for example? Biologists know the seminal fluid
contains some white blood cells that can be infected with the virus, but
what about sperm themselves? Virginia Scofield, Bhashini Rao and others
at the University of California, Los Angeles, believe that HIV may be able
to hitch a lift on the surface of sperm in order to reach the cells it can
infect. Under an electron microscope, the team says, HIV can be seen attached
to the surface of sperm cells.

Scofield and her colleagues suggest that sperm can also bind to cells
that HIV infects, with the help of molecules of the immune system known
as HLA antigens. Cells carrying these antigens are common in the vagina.
Scofield and her colleagues believe that this bond between the sperm and
the cell may help the virus to enter and infect the cells.

Other researchers dispute these findings. Jeffrey Pudney from Brigham
and Women’s Hospital, Boston, has tried to detect HIV in sperm using many
different analytical techniques, and failed.

Not for the first time, scientists debated whether saliva is infectious.
Haseltine’s team said that, as dendritic cells are present in the mucous
membranes of the mouth as well as those of the vagina and rectum, there
is a ‘theoretical possibility’ of spreading HIV by kisses that exchange
saliva.

However, a group of researchers from the Pennsylvania School of Dental
Medicine in Philadelphia incubated HIV in saliva from healthy HIV-negative
volunteers and found that the saliva could inhibit replication of the virus.
The greater the concentration of saliva, the more inhibited the virus. Saliva
may contain an ‘inhibitory factor’ against HIV, says the team – and this
factor seems to be specific to HIV.